One of the hurdles encountered by immunotherapy attempts for type 1 diabetes (T1D) is the delicate ethical issue of minimizing
risks for a disease with a normal life expectancy in many patients. For this reason, antigen (Ag)-specific immunotherapies
are attractive in view of their selectivity and favorable safety profile (1). However, they have not met expectations in therapeutic trials using insulin (2–4) and GAD (5). These trials face several technical difficulties: the need to produce and administer proteins of suitable quality and quantity;
bioavailability issues, as prolonged delivery of small Ag amounts may be more effective at restoring long-term immune tolerance;
routes of administration, with the noninvasive oral route being more tolerogenic but suffering considerable Ag degradation;
and Ag delivery in a noninflammatory environment to avoid unwanted immunogenic outcomes. The most important issue is the timing
of immune intervention, with a panoply of agents effective at preventing disease even in the reductionist NOD mouse model,
but only a handful working at reversing established disease, which is the preferred setting for human trials.

In this issue, Robert et al. (6) bring Ag-specific therapies into a new dimension by letting genetically modified Lactococcus lactis do the job. L. lactis is a nonpathogenic, noncolonizing, commensal bacterium with a long safety record in the dairy industry. Biological containment
of genetically modified strains to avoid environmental propagation can be obtained …